Study of vesicular stomatitis virus leads to model of viral assembly process
Vesicular stomatitis virus, or VSV, has long been a model system for studying and understanding the life cycle of negative-strand RNA viruses, which include viruses that cause influenza, measles and rabies.
More importantly, research has shown that VSV has the potential to be genetically modified to serve as an anti-cancer agent, exercising high selectivity in killing cancer cells while sparing healthy cells, and as a potent vaccine against HIV.
For such modifications to occur, however, scientists must have an accurate picture of the virus's structure. While three-dimensional structural information of VSV's characteristic bullet shape and its assembly process has been sought for decades, efforts have been hampered by technological and methodological limitations.
Now, researchers at UCLA's California NanoSystems Institute and the UCLA Department of Microbiology, Immunology and Molecular Genetics and colleagues have not only revealed the 3-D structure of the trunk section of VSV but have further deduced the architectural organization of the entire bullet-shaped virion through cryo-electron microscopy and an integrated use of image-processing methods.
Their research findings appear this month in the journal Science.
"Structures of individual rhabdovirus proteins have been reported in Science and other high-profile journals, but until now, how they are organized into a bullet shape has remained unclear," said study author Z. Hong Zhou, UCLA professor of microbiology, immunology and molecular genetics and a member of the CNSI. "The special shape of VSV-- a bullet head with a short, helical trunk-- has lent to its evasion from three-dimensional structural studies."
Based on their research into the structure of VSV, the team proposed a model for the assembly of the virus, with its origin at the bullet tip. Their data suggest that VSV assembles through the alternating use of several possible interaction interfaces coded in viral protein sequences to wind its protein and RNA chain into the characteristic bullet shape.